Interpretive Handbook

Test
82920 :
Cortisol, Free, Random, Urine

Cortisol is a steroid hormone synthesized from cholesterol by a multienzyme cascade in the adrenal glands. It is the main glucocorticoid in humans and acts as a gene transcription factor influencing a multitude of cellular responses in virtually all tissues. Cortisol plays a critical role in glucose metabolism, maintenance of vascular tone, immune response regulation, and in the body's response to stress. Its production is under hypothalamic-pituitary feedback control.

Only a small percentage of circulating cortisol is biologically active (free), with the majority of cortisol inactive (protein bound). As plasma cortisol values increase, free cortisol (ie, unconjugated cortisol or hydrocortisone) increases and is filtered through the glomerulus. Urinary free cortisol (UFC) correlates well with the concentration of plasma free cortisol. UFC represents excretion of the circulating, biologically active, free cortisol that is responsible for the signs and symptoms of hypercortisolism.

UFC is a sensitive test for the various types of adrenocortical dysfunction, particularly hypercortisolism (Cushing syndrome). A measurement of 24-hour UFC excretion, by liquid chromatography-tandom mass spectrometry (LC-MS/MS), is the preferred screening test for Cushing syndrome. LC-MS/MS methodology eliminates analytical interferences including carbamazepine (Tegretol) and synthetic corticosteroids, which can affect immunoassay-based cortisol results.

Most patients with Cushing syndrome have increased 24-hour urinary excretion of cortisol. Further studies, including suppression or stimulation tests, measurement of serum corticotropin (adrenocorticotropic hormone) concentrations, and imaging are usually necessary to confirm the diagnosis and determine the etiology.

Values in the normal range may occur in patients with mild Cushing syndrome or with periodic hormonogenesis. In these cases, continuing follow-up and repeat testing are necessary to confirm the diagnosis.

Patients with Cushing syndrome due to intake of synthetic glucocorticoids should have suppressed cortisol. In these circumstances a synthetic glucocorticoid screen might be ordered (SGSU / Synthetic Glucocorticoid Screen, Urine).

Suppressed cortisol values may also be observed in primary adrenal insufficiency and hypopituitarism. The optimal specimen type for evaluation of primary adrenal insufficiency and hypopituitarism is serum (CORT / Cortisol, Serum).